The development and progression of the autoimmune disease is a complex process due to imbalance in regulation of many active cytokines. Tumor necrosis factor-α (TNF-α) has been shown to play an important role in immune regulation among numerous cytokines. However, its overexpression has been demonstrated to be one of the main causes of autoimmune diseases etc. Accordingly, use of biopharmaceuticals suppressing TNF-α activity become one of the most successful therapies for the treatment of such diseases. Indications which have been approved mainly encompass rheumatoid arthritis, Crohn's disease, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, and juvenile idiopathic arthritis, while a variety of other related diseases are subjected to clinical trials.
Currently, in European and American market, pharmaceutical anti-TNF-α antibodies and antibody-like Fc fusion protein drugs, such as REMICADE® (infliximab), have been available. But REMICADE® has a shorter half-life in vivo of approximately 9 days. In addition, although REMICADE® has good binding affinity, bioactivity, and clinical efficacy, as a chimeric antibody consisting of ⅓ of murine-derived sequences and ⅔ of human-derived sequences, about 10%-47% of patients appear an immune response after administration of REMICADE®, generally resulting in the production of human anti-mouse antibodies (HAMA), which affects the potency and long-term application of the antibody. Accordingly, there is a great need for an anti-TNF-α antibody with higher degree of humanization and maximally reduced proportion of the murine-derived sequences to decrease the degree of murine origin and allow safe usage in treating diseases in human. A common process for humanizing an antibody is to graft parts of the complementary-determining regions (CDRs) of the variable regions (VH, VK) of a murine-derived antibody into the framework regions of a previously selected human antibody. The resultant antibody will consist mostly of human-derived sequences and be able to retain the selectivity of the starting antibody of murine origin for the same antigen. However, the process generally leads to loss of the antibody affinity.